BAFF (B cell-activating factor in the TNF family), also known as BLyS, TALL-1, THANK, and zTNF4, is implicated a number of autoimmune and lymphoproliferative disorders. For a review, see, e.g., Kalled et al., Curr. Dir. Autoimmun. 8:206-242 (2005). BAFF is expressed in macrophages, monocytes, dendritic cells and T cells and is critical for the survival of B cells. Moore et al., Science 285:260-263 (1999); Mukhopadhyay et al., J Biol. Chem. 274:15978-15981(1999); Gross et al., Nature 404:995-999 (2000); Shu et al., J. Leukoc. Biol. 65:680-683 (1999). BAFF is a type II transmembrane protein that can be proteolytically cleaved between Arg 133 and Ala 134 and released as a soluble protein. Moore et al., Science 285:260-263 (1999); Schneider et al., J. Exp. Med. 189:1747-1756 (1999). To date, three receptors for BAFF have been identified: TACI, BCMA, and BR3 (also known as BAFF-R).
In vivo, BAFF can exist as a transmembrane protein or a soluble protein, and can be bound or unbound to a receptor. Thus, BAFF is distributed among a variety of pools, including free soluble BAFF, receptor-bound soluble BAFF, transmembrane BAFF, and receptor-bound transmembrane BAFF.
Excess BAFF has been implicated in several disease states, including Sjogren's Syndrome, rheumatoid arthritis and lupus (reviewed in Kalled, 2005, Immunol Rev. 204:43-54). Some known methods for detection of BAFF in biological samples utilize antibodies that detect unbound BAFF (e.g., free soluble BAFF, e.g., in serum). However, because BAFF may also be complexed with receptor, such methods do not identify those patients that may have normal levels of unbound BAFF but may have abnormal BAFF distribution or abnormal or increased levels of receptor-bound BAFF or membrane bound BAFF and/or total BAFF. New methods are needed to identify such patients, e.g., as candidates for therapy (e.g., anti-BAFF therapy) and/or to monitor such patients (e.g., for BAFF response).